Aα-Val360: a marker of neutrophil elastase and COPD disease activity

Forced expiratory volume in 1 s is currently the most widely used marker of chronic obstructive pulmonary disease (COPD) severity; however, it is a poor surrogate of the emphysematous component and the underlying pathophysiological mechanism, and therefore new markers are urgently needed. Neutrophil elastase (NE) is likely to play a key pathophysiological role in COPD and the current study explores a marker of NE activity as a potential indicator of COPD disease activity. Aα-Val(360) was measured in 81 subjects with a clinical diagnosis of COPD, both in the stable state and at presentation with an acute exacerbation, and comparisons were made using lung function tests and computed tomography imaging. The relationship of Aα-Val(360) with disease progression was also assessed in 40 of the subjects over a 4-yr period. Baseline Aα-Val(360) related to physiological and radiological markers of disease severity, was higher at presentation with an acute exacerbation than in the stable state and (at least partly) related to disease progression over the subsequent 4 yrs. We demonstrate that Aα-Val(360) is a marker of cross-sectional COPD disease severity and possibly disease progression, and represents a new concept of specific biomarkers. This study therefore reports the first in vivo data to support the pathophysiological role of NE in COPD.